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2009 Grants - Lee

Effect and Mechanism of Cell Cycle Re-entry in Neurodegeneration

Hyoung-gon Lee, Ph.D.
Case Western Reserve University
Cleveland, Ohio

2009 New Investigator Research Grant

Nearly all cells exhibit a cycle of growth in which cell division (when one cell divides into two new cells) alternates with periods of non-dividing activity. Nerve cells exhibit this cycle in early development, but then biochemical mechanisms turn off the cycle, allowing the nerve cells to form the unique structures and capabilities of the brain. There is some evidence, however, that nerve cells in the Alzheimer brain undergo biochemical changes causing them to attempt to return to the cycle of cell division. Unfortunately when mature nerve cells return to the cell division cycle, they die.

At this time, it is not known whether return to the cell division cycle is the main cause of neurodegeneration in Alzheimer's disease, or whether other biochemical changes are also involved. Hyuong-gon Lee, Ph.D. and colleagues are studying how nerve cells return to the cell division cycle and the role of that process in neurodegeneration. The researchers are focusing on a protein known as the retinoblastoma protein (Rb), which normally stops cells from dividing. There is evidence that this protein may be inhibited in the brain in Alzheimer's disease. Therefore, Dr. Lee's team has generated a mouse model that has been genetically altered so that the researchers can turn off expression of the Rb protein in one region of the brain.

Using their mouse model, the researchers will determine if allowing nerve cells to return to the cell division cycle causes neurodegeneration. They will also examine if this effect produces the characteristic brain pathology seen in Alzheimer's disease. These studies will help to address a fundamental question about the causes of nerve cell death in the early stages of Alzheimer's disease, and they may suggest ways to prevent such cell death.